In this program, expert faculty discuss data presented at the 2023 ACC Congress in a concise, informative, on-demand format. This format extends the congress analysis to a broader audience with greater detail than what is available in abstracts. Rapid advances from the meeting require well-planned educational programming to bridge knowledge, competence, and performance gaps.
CLEAR Outcomes Trial and Cardiovascular Outcomes
CLEAR Outcomes Trial and Cardiovascular Outcomes
Welcome to CME on ReachMD. This episode is part of our MinuteCME curriculum.
Prior to beginning the activity, please be sure to review the faculty and commercial support disclosure statements as well as the learning objectives.
I'm Dr. Steven Nissen. I am the Chief Academic Officer of the Heart, Vascular, Thoracic Institute at the Cleveland Clinic. And I'm going to talk with you about the CLEAR Outcomes trial.
This is a trial performed in patients that were statin intolerant, and they had to complain of intolerance to two or more statins, or one statin if unwilling to attempt a second statin, or advised by a physician not to attempt a second statin. The patients were either primary or secondary prevention patients with an LDL cholesterol greater than 100, randomize to bempedoic acid 180 milligrams per day or matching placebo. This was an event-driven trial to 1,620 primary 4-component MACE endpoints. And 810 3-component MACE endpoints with greater than 24 months of follow-up.
The primary and key secondary endpoints are shown here. The primary endpoint was 4-component MACE, nonfatal MI, nonfatal stroke, coronary revascularization, or cardiovascular death. There was hierarchical testing of the key secondary endpoints to preserve study wise alpha at 0.5. That included 3-component MACE, nonfatal and fatal MI, coronary revascularization, fatal and nonfatal stroke, cardiovascular death, and all-cause mortality.
The baseline characteristics, importantly, 48% of these patients were women. We had 30% high-risk primary prevention, and 70% secondary prevention, nearly half were diabetic. The drug, bempedoic acid, reduced LDL cholesterol at the 6-month point, which was where we specified we would measure by 21.7%. The drug also reduced high sensitivity CRP by 22%. The LDL differences between placebo and bempedoic acid narrowed over time but maintained a gradient between the two treatment arms.
This is the primary and first key secondary endpoint, 4-component MACE had a hazard ratio of 0.87 with a P-value of 0.004. Number needed to treat was 63 to prevent one event, and the Kaplan-Meier curve was separated early. 3-component mace had a hazard ratio of 0.85, P was 0.006 with an absolute risk reduction of 1.3%. The big effect was on fatal and nonfatal MI, which was reduced 23%, hazard ratio of 0.77, also highly significant. On the right, coronary revascularization, that's stenting or bypass surgery, hazard ratio of 0.81, highly significant.
There was no effect of the trial regimens on either cardiovascular death or all-cause mortality. All of the recent trials over the last decade of LDL-lowering therapies have failed to show an effect on mortality. Presumably this is because our conjunctive therapies are particularly effective, and death is a late effect of coronary disease events; doesn't occur after the first MI but may occur after the second or third myocardial infarction.
There were some adverse events, but importantly, these patients who were statin intolerant did not withdraw from the bempedoic acid group in a higher rate than the placebo group. Importantly, new-onset diabetes was not more common. As you know, in statin trials, there was an increase in the risk of diabetes that was not observed with bempedoic acid. There was a 1% absolute increase in gout and a 1% absolute increase in cholelithiasis.
So what did we conclude? Bempedoic acid was well tolerated in a mixed population of primary and secondary prevention patients unable or unwilling to take a statin. The drug lowered LDL cholesterol by 21.7% and CRP by 22.2%, with small increases in the incidence of gout and cholelithiasis. The primary endpoint 4-component MACE was reduced by 13%; 3-component MACE by 15%, myocardial infarction by 23%, and coronary revascularization by 19%. These findings established bempedoic acid as an effective approach to reduce major cardiovascular events in statin-intolerant patients.
Thank you for your attention.
You have been listening to CME on ReachMD. This activity is jointly provided by Global Learning Collaborative (GLC) and TotalCME, Inc. and is part of our MinuteCME curriculum.
To receive your free CME credit, or to download this activity, go to ReachMD.com/CME. Thank you for listening.
This activity has been designed to meet the educational needs of the interprofessional team, including clinical cardiologists and interventional cardiologists, as well as critical care, emergency medicine, hospital medicine, interventional radiology, vascular surgeons, vascular medicine specialists, and primary care physicians. It will also include nurses, nurse practitioners, physician assistants, pharmacists, and any HCPs involved in the care and/or treatment of cardiovascular patients.
After participating in this educational activity, participants should be better able to:
- Evaluate recent practice-changing data that can be applied to practice and patients
- Apply recently presented data into clinical practice to expand treatment options and improve patient outcomes
- Discuss new data on novel agents and therapeutic approaches for patients with application in the community setting
In support of improving patient care, this activity has been planned and implemented by Global Learning Collaborative (GLC) and TotalCME, Inc. GLC is jointly accredited by the American Council for Continuing Medical Education (ACCME), the Accreditation Council for Pharmacy Education (ACPE) and the American Nurses Credentialing Center (ANCC) to provide continuing education for the healthcare team.
This activity was planned by and for the healthcare team, and learners will receive 1.25 Interprofessional Continuing Education (IPCE) credits for learning and change.
In accordance with the ACCME Standards for Integrity and Independence, Global Learning Collaborative (GLC) requires that individuals in a position to control the content of an educational activity disclose all relevant financial relationships with any ineligible company. GLC mitigates all conflicts of interest to ensure independence, objectivity, balance, and scientific rigor in all educational programs.
The following faculty have disclosed:
Marius Hoeper, MD, faculty for this educational event, receives consulting fees from Acceleron, Actelion, AOP Health, Bayer, Ferrer, GSK, Janssen, and MSD.
Steven Nissen, MD, MACC, faculty for this educational event, receives research funds from Abbvie, AstraZeneca, Amgen, Bristol Myers Squibb, Eli Lilly, Esperion, Medtronic, MyoKardia, New Amsterdam Pharmaceuticals, Novartis, Pfizer, and Silence Therapeutics.
Kelly Chin, MD, faculty for this educational event, receives research funds from Acceleron, Altavant, Gossamer Bio, Janssen, Merck, Pfizer and United Therapeutics; and receives consulting fees from Arena, Acceleron and Shouti.
Christie Mitchell Ballantyne, MD, faculty for this educational event, receives research funds from Abbott Diagnostic, Akcea, Amgen, Arrowhead, Esperion, Ionis, Merck, New Amsterdam, Novartis, Novo Nordisk, Regeneron, and Roche Diagnostic; and receives consulting fees from 89Bio, Abbott Diagnostics, Alnylam
Pharmaceuticals, Althera, Amarin, Amgen, Arrowhead, Astra Zeneca, Denka Seiken, Esperion, Genentech, Gilead, Illumina, Matinas, BioPharma Inc, Merck, New Amsterdam, Novartis, Novo Nordisk, Pfizer, Regeneron, and Roche Diagnostic.
R. Kevin Rogers, MD, MSc, RPVI, faculty for this educational event, has no relevant financial relationships with ineligible companies.
Marc P. Bonaca, MD, MPH, FAHA, FACC, faculty for this educational event, receives research funds from Abbott Laboratories, Adamis Pharmaceuticals Corporation, Agios Pharmaceuticals, Inc., Alexion Pharma, Alnylam Pharmaceuticals, Inc., Amgen Inc., Angionetics, Inc., ARCA Biopharma, Inc., Array BioPharma, Inc., AstraZeneca and Affiliates, Atentiv LLC, Audentes Therapeutics, Inc., Bayer and Affiliates, Beth Israel Deaconess Medical Center, Better Therapeutics, Inc., BIDMC, Boston Clinical Research Institute, Bristol-Meyers Squibb Company, Cambrian Biopharma, Inc., Cardiol Therapeutics Inc., CellResearch Corp., Cook Medical Incorporated, Covance, CSL Behring LLC, Eidos Therapeutics, Inc., EP Trading Co. Ltd., EPG Communication Holdings Ltd., Epizon Pharma, Inc., Esperion Therapeutics, Inc., Everly Well, Inc., Exicon Consulting Pvt. Ltd., Faraday Pharmaceuticals, Inc., Foresee Pharmaceuticals Co. Ltd., Fortress Biotech, Inc., HDL Therapeutics Inc., HeartFlow Inc., Hummingbird Bioscience, Insmed Inc., Ionis Pharmaceuticals, IQVIA Inc., JanOne Biotech Holdings Inc., Janssen and Affiliates, Kaneka, Kowa Research Institute, Inc., Kyushu University, Lexicon Pharmaceuticals, Inc., LSG Kyushu University, Medimmune Ltd., Medpace, Merck & Affiliates, Novartis Pharmaceuticals Corp., Novate Medical, Ltd., Novo Nordisk, Inc., Pan Industry Group, Pfizer Inc., PhaseBio Pharmaceuticals, Inc., PPD Development, LP, Prairie Education and Research Cooperative, Prothena Biosciences Limited, Regeneron Pharmaceuticals, Inc., Regio Biosciences, Inc., Rexgenero, Sanifit Therapeutics S.A., Sanofi-Aventis Groupe, Silence Therapeutics PLC, Smith & Nephew plc, Stealth BioTherapeutics Inc., State of Colorado CCPD Grant, The Brigham & Women's Hospital, Inc., The Feinstein Institutes for Medical Research, Thrombosis Research Institute, University of Colorado, University of Pittsburgh, VarmX, Virta HealthCorporation, WCT Atlas, Worldwide Clinical Trials Inc., WraSer, LLC,Yale Cardiovascular Research Group, and AHA SFRN; receives consulting fees from Audentes; and has an ownership interest in Medtronic and Pfizer.
Marat Fudim, MD, MHS, faculty for this educational event, receives consulting fees from Merck.
Cynthia M. Westerhout, PhD, faculty for this educational event, receives consulting fees from Bayer Canada.
Stephen J. Greene, MD, FACC, FHFSA, faculty for this educational event, receives research funds from AstraZeneca, Amgen, Cytokinetics, Pfizer, Merck, Novartis, Sanofi, Bristol Myers Squibb; and receives consulting fees from AstraZeneca, Amgen, Bayer, Boehringer Ingelheim, Cytokineteics, Merck, PharmaIN, Roche Diagnostics, Sanofi, Tricog Health, Urovant Pharmaceuticals, CSL Vifor and scPharmaceuticals.
Ahmad Masri, MD, MS, faculty for this educational event, receives research funds from Pfizer, Ionis/Akcea, Attralus, Cytokinetics, Ultromics and the Wheeler Foundation; and receives consulting fees from Cytokinetics, BMS, Eidos, Pfizer, Ionis, Lexicon, Alnylam, Attralus, Haya, Intellia and Tenaya.
The following planners/reviewers/managers have disclosed:
Prerna Poojary, PhD, planner for this educational event, has no relevant financial relationships with ineligible companies.
William Mencia, MD, FACEHP, CHCP, reviewer for this educational event, has no relevant financial relationships with ineligible companies.
TotalCME, Inc. planners and managers have no relevant commercial relationships to disclose.
All the relevant financial relationships for these individuals have been mitigated.
The views and opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of GLC and TotalCME, Inc. This presentation is not intended to define an exclusive course of patient management; the participant should use his/her clinical judgment, knowledge, experience, and diagnostic skills in applying or adopting for professional use any of the information provided herein. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient's conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. Links to other sites may be provided as additional sources of information. Once you elect to link to a site outside of MedEd On The Go you are subject to the terms and conditions of use, including copyright and licensing restrictions, of that site.
Reproduction of this material is not permitted without written permission from the copyright owner.
This activity is supported by independent educational grants from Janssen Scientific Affairs, LLC, Merck Sharp & Dohme Corp and Cytokinetics, Incorporated.
Jointly provided by Global Learning Collaborative (GLC) and TotalCME, Inc.
This activity is FREE to all participants.
During the period 3/27/2023 through 3/27/2024, registered participants wishing to receive continuing education credit for this activity must follow these steps:
- Read the learning objectives and faculty disclosures.
- Answer a pre-program question.
- View the program.
- Complete the post-test with a score of 100%.
- Complete activity evaluation.
- Apply for credit and either bank your credits or print your certificate.
For Pharmacists: Upon successfully completing the post-test with a score of 100% and the activity evaluation form, transcript information will be sent to the NABP CPE Monitor Service. This may require you to add or update the e-profile ID/date of birth information saved in your account.
Our site requires a computer, tablet, or mobile device and a connection to the Internet. For best results, a high-speed Internet connection is recommended (DSL/Cable/Fibre). We also recommend using the latest version of your favorite browser to ensure compliance with W3C standards, such as Chrome, Safari, Firefox, or Microsoft Edge.